Blocking apoptosis prevents blindness in Drosophila retinal degeneration mutants.
Apoptosis is a gene-directed form of cell death that is essential for normal development and health. Yet abnormally high levels of apoptosis are linked to many degenerative diseases. Some important biochemical events in apoptosis have been identified, but the therapeutic utility of blocking cell death remains unclear. An important question in this regard is whether cells rescued from apoptosis can function. We have investigated the mechanism of cell death in two Drosophila mutant strains that exhibit age-related retinal degeneration. One of these mutations also occurs in humans, where it causes retinitis pigmentosa. We found that retinal cell death in rdgC and ninaE(RH27)/+ flies occurred by apoptosis and was blocked by eye-specific expression of the baculoviral cell survival protein p35. Most importantly, the mutant flies expressing p35 showed significant retention of visual function. The results demonstrate a therapeutic benefit of late-stage inhibition of apoptosis to flies, and suggest that similar results may be obtained in higher organisms.
Davidson
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Howard Hughes Medical Research Institute, Massachusetts Institute of Technology, Cambridge 02139, USA.
Steller
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D000818:Animals; D017209:Apoptosis; D004330:Drosophila / Q000235:genetics; D004596:Electroretinography; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D009154:Mutation; D017956:Photoreceptor Cells, Invertebrate / Q000648:ultrastructure*; D014764:Viral Proteins / Q000494:pharmacology; D014785:Vision, Ocular
D051034:Inhibitor of Apoptosis Proteins; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus